Senate Republicans’ bill to erase major parts of the Affordable Care Act would cause an estimated 22 million more Americans to be uninsured by the end of the coming decade, while reducing federal spending by $321 billion during that time, according to the Congressional Budget Office.

The forecast issued Monday by Congress’s nonpartisan budget scorekeepers appeared to rapidly erode Republicans’ confidence in the bill, with at least four GOP lawmakers saying by the evening that they would vote against even starting debate on it.

By late Monday, several senators and aides appeared nervous and unsure about the path forward. They hedged on the timing of that procedural vote and suggested the workweek could stretch beyond Friday. Still, there was some hope for salvaging the effort, and GOP leaders were still looking for ways to make last-minute changes that might garner crucial support.

The projection of uninsured numbers and federal spending had been awaited as a crucial piece of evidence while McConnell (Ky.) and other Republican leaders try to hurry a vote on the bill this week. They already were navigating an expanding minefield of criticism from their party’s moderate and conservative wings.

The release of the 49-page CBO ­report late Monday afternoon seemed to worsen the bill’s prospects. No new senators immediately said they would back the legislation, and Sens. Susan Collins (Maine), Rand Paul (Ky.) and Ron Johnson (Wis.) signaled that they would vote against starting debate Tuesday on the bill in its current form. A fourth senator, Dean Heller (R-Nev.), had expressed his opposition last week.

Collins, a moderate Republican, tweeted that the measure would “hurt [the] most vulnerable Americans” and failed to solve the problems of access to care in rural Maine where, she wrote, “hospitals are already struggling.”

The Senate bill could undergo further changes before such a vote is scheduled, which could prompt these senators to reconsider. But if the Democrats vote as a bloc, McConnell can afford to lose no more than two Republicans for a procedural motion to succeed.

Asked whether McConnell and other Senate leaders had amassed enough support to pass the measure, Sen. Roy Blunt (R-Mo.) responded, “Anyone would tell you they don’t.”

The CBO estimated that two-thirds of the drop in health coverage a decade from now would fall on low-income people who rely on Medicaid. And among the millions now buying private health plans through ACA marketplaces, the biggest losers would roughly parallel those under legislation passed recently by the House: The sharpest spike in insurance premiums would fall on middle-aged and somewhat older Americans.

Its analysis of the Senate measure’s impact on federal spending — $321 billion saved over a decade — compared with $119 billion for the House’s version.

See where the Senate health-care bill’s subsidy cuts will affect Americans most

Paul labeled the Better Care Reconciliation Act “a terrible bill” and repeated his contention that it would not go far enough in repealing the sprawling health-care law enacted seven years ago by a Democratic Congress and president.

McConnell took to the Senate floor just before the report’s release to press anew for rapid action. He made it clear that the bill, already tweaked early Monday, could be negotiated further to try to win over holdouts.

“The American people need better care right now,” McConnell said. “This legislation includes the necessary tools to provide it.”

Democrats quickly seized on the CBO’s projection of how much the ranks of the uninsured would grow.

“Republicans would be wise to read it as a giant stop sign,” Senate Minority Leader Charles E. Schumer (D-NY) told reporters. “No matter how the bill changes around the edges, it is fundamentally rotten at the center.”

Former CBO director Doug Holtz-Eakin, a Republican who is now president of the American Action Forum, said the report draws basically the same conclusions as the budget office’s earlier analysis of the House measure. He predicted that GOP senators are “going to get beaten on the head with the CBO report like it’s a club.”

The fresh figures come as President Trump, in a sharp pivot from the praise he initially lavished on the House bill, has been urging the Senate to provide Americans more generous help with health insurance. On Sunday, the president repeated during a “Fox and Friends” TV appearance a word he had used in a private White House lunch with a group of GOP senators earlier this month: that the House’s version is “mean.”

On Monday, the White House again sought to cast doubt on the budget office’s credibility. “The CBO has consistently proven it cannot accurately predict how healthcare legislation will impact insurance coverage,” it said in a statement. “This history of inaccuracy, as demonstrated by its flawed report on coverage, premiums, and predicted deficit arising out of Obamacare, reminds us that its analysis must not be trusted blindly.”

According to the latest report, the Senate bill would mean that an estimated 15 million fewer Americans would have coverage next year, compared with the number if the ACA, commonly called Obamacare, remained in place. At the end of the decade, the 22 million increase in the ranks of the uninsured would include 15 million low-income Americans who would otherwise be on Medicaid and 7 million with private insurance. That total is about a million less than the 2026 impact of the House plan.

The Senate plan would reduce federal spending to help people afford premiums for individual health insurance policies significantly more than under the House version. The Senate’s version would cut spending on tax credits by $408 billion by 2026 — compared with a $276 billion reduction in the House plan. The difference lies, in part, because the Senate’s version would not permit people with incomes as high to qualify for tax credits and would restrict federal help to health plans sold through the ACA’s marketplaces. The Senate would tie the tax credits to skimpier health plans than the current subsidies.

And while the Senate bill would phase out the ACA’s Medicaid expansion more slowly than the House legislation, cuts to the public insurance program for the poor still would account for by far the largest share of the reduction in federal spending under the Senate bill — $772 billion over the coming decade. In a briefing for reporters, CBO staff members said that they had not analyzed the bill’s effects on Medicaid cuts beyond the coming decade but that the reductions inevitably would be greater for a second decade.

While they differ in important details, both the Senate GOP’s plan and the American Health Care Act narrowly passed by House Republicans in May share the goal of undoing central aspects of the ACA.

Both bills would eliminate enforcement of the law’s mandate that most Americans carry health insurance, relying on subtler deterrents to keep people from dropping coverage. The House version would let insurers temporarily charge higher rates to those who let their coverage lapse, while the Senate added a provision Monday that would let health plans freeze out customers for six months if they let it lapse.

In different ways, both would replace federal subsidies that help the vast majority of consumers buying coverage through ACA marketplaces, instead creating smaller tax credits that would provide greater assistance to younger adults while making insurance more expensive for people from middle age into their 60s.

After two years, both also would end subsidies that now help about 7 million lower-income people with ACA health plans afford deductibles and copays. And both would repeal an array of taxes that have helped to pay for the ACA’s benefits, including levies on health insurers and on wealthy Americans’ investment income.

For the Senate bill, the CBO’s estimates of insurance coverage and federal spending are influenced by the fact that its forecast covers a 10-year window and the legislation’s most profound changes for the nation’s health-care system are tilted toward the latter part of that period.

The bill would, for instance, leave in place the ACA’s expansion of Medicaid through 2020. After that, it would begin a three-year phaseout of the federal money that under the ACA has paid almost the entire cost of adding 11 million Americans to the program’s rolls in 31 states.

That means the extra funding wouldn’t disappear until the mid-2020s — roughly when sharp new restrictions on federal payments for the entire Medicaid program would take effect.

Over the weekend, the senior Democrat on the Senate subcommittee that oversees the CBO said in a tweet that he had asked the budget office to estimate the Senate bill’s effect on insurance coverage over a longer time horizon. “GOP is hiding the worst Medicaid cuts in years 11, 12, 13 and hoping CBO stays quiet,” Sen. Chris Murphy (D-Conn.) wrote.